6in7 | pdb_00006in7
Crystal structure of AlgU in complex with MucA(cyto)
Structural highlights
Function[MUCA_PSEAE] Negative regulator of the sigma factor AlgU. Plays a role in the differentiation of P.aeruginosa into the alginate-producing form. Inactivation of mucA causes a switch from the non-mucoid to mucoid state resulting in constitutive expression of alginate biosynthetic genes. [RPSH_PSEAE] Sigma factors are initiation factors that promote the attachment of RNA polymerase to specific initiation sites and are then released. This sigma factor regulates genes such as algD, involved in alginate biosynthesis. Publication Abstract from PubMedAlginate production in Pseudomonas aeruginosa is regulated by the alternate sigma factor AlgU, which in turn is regulated by the MucABCD system. The anti-sigma factor MucA binds AlgU in the cytoplasm and prevents AlgU from binding to the RNA polymerase for transcription. MucB binds MucA in the periplasm and inhibits proteolysis of MucA and subsequent release of AlgU. In this work, we report crystal structures of MucA in complex with AlgU and MucB. A structure of MucB alone reveals the structural changes required for MucA recognition. A unique disulfide bond is identified in MucB, and mutation of this disulfide bond results in a shift from monomer to MucB dimers or tetramers. As MucB tetramers have previously been shown to be unable to bind MucA, this suggests a redox-sensitive stress response mechanism in MucB. The AlgU-MucA structure reveals a conserved sigma factor/anti-sigma factor complex, but AlgU lacks a disulfide bond conserved in many other sigma factors. Our structures reveal the molecular basis for MucA recognition by MucB in the periplasm and AlgU in the cytoplasm, thus providing an important step in understanding the mechanisms that regulate a key signal transduction pathway involved in P. aeruginosa pathogenesis. DATABASE: The atomic coordinates and structure factors for MucAcyto -AlgU, MucB, and MucAperi -MucB have been deposited in the Protein Data Bank (PDB) with the accession code 6IN7, 6IN8, and 6IN9, respectively. Structural basis for the recognition of MucA by MucB and AlgU in Pseudomonas aeruginosa.,Li S, Lou X, Xu Y, Teng X, Liu R, Zhang Q, Wu W, Wang Y, Bartlam M FEBS J. 2019 Jul 11. doi: 10.1111/febs.14995. PMID:31297938[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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